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Improvement of secondary metabolite production in Streptomyces by manipulating pathway regulation

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Abstract

Titer improvement is a constant requirement in the fermentation industry. The traditional method of “random mutation and screening” has been very effective despite the considerable amount of time and resources it demands. Rational metabolic engineering, with the use of recombinant DNA technology, provides a novel, alternative strategy for titer improvement that complements the empirical method used in industry. Manipulation of the specific regulatory systems that govern secondary metabolite production is an important aspect of metabolic engineering that can efficiently improve fermentation titers. In this review, we use examples from Streptomyces secondary metabolism, the most prolific source of clinically used drugs, to demonstrate the power and utility of exploiting natural regulatory networks, in particular pathway-specific regulators, for titer improvement. Efforts to improve the titers of fredericamycin, C-1027, platensimycin, and platencin in our lab are highlighted.

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Acknowledgements

Studies on natural product biosynthesis and engineered described from the Shen laboratories were supported in part by the National Institutes of Health (NIH) grants CA78747, CA106150, and CA113297. M.J.S. is supported in part by NIH grant T32 GM008347.

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Authors and Affiliations

  1. Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI, 53705-2222, USA

    Yihua Chen

  2. Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, 53705-2222, USA

    Michael J. Smanski

  3. Division of Pharmaceutical Sciences, University of Wisconsin National Cooperative Drug Discovery Group, and Department of Chemistry, University of Wisconsin-Madison, 777 Highland Ave, Madison, WI, 53705-2222, USA

    Ben Shen

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  1. Yihua Chen
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Correspondence to Ben Shen.

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Chen, Y., Smanski, M.J. & Shen, B. Improvement of secondary metabolite production in Streptomyces by manipulating pathway regulation. Appl Microbiol Biotechnol 86, 19–25 (2010). https://doi.org/10.1007/s00253-009-2428-3

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  • DOI: https://doi.org/10.1007/s00253-009-2428-3

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